Selective enrichment and detection of PD-L1 positive extracellular vesicles derived from human plasma and patient derived tumor cells

• Published in: Sensors and actuators. B, Chemical Chemical, 2023-02, Vol.377, p.133086, Article 133086
• Main Authors: Ren, Yongan, Ge, Ke, Lu, Wei, Peng, Wenbo, Che, Haiyan, Ma, Jianxin, Jia, Changku, Yao, Bo
• Format: Article
• Language: English
• Subjects: Extracellular vesicles; Human plasma; PD-L1; Primary tumor cells; TdT reaction
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2022.133086

Recent studies reported that the level of PD-L1 carried by extracellular vesicles (EVs) could distinguish the presence of tumors and had a good correlation with the response to immunotherapy. In this manuscript, we developed an EV-TdT assay for isolation and detection of PD-L1+ EVs. PD-L1+ EVs were directly captured from biological samples by PD-L1 antibodies immobilized on the magnetic beads (MBs), then combined with cholesterol modified DNA probes, which initiated the terminal deoxynucleotidyl transferase (TdT) to amplify the signal of PD-L1+ EVs. The EV-TdT assay enables selective enrichment of PD-L1+ EVs in low-content samples, such as blood and excreta of small amounts of primary tumor cells. Moreover, it can evaluate the relative abundance of PD-L1+ EVs in the total population, by this way, we observed that PD-L1+ EVs were more abundant in the extracellular microenvironment of primary tumor cells than in human plasma, indicating that quite a bit of PD-L1+ EVs were derived from tumor cells. The EV-TdT assay has been proven a practical method for detection of PD-L1+ EVs and is greatly potential as an alternative to existing assays for screening immunotherapy benefit populations.